The administrative component of this PSO (PPG) will have both scientific and organizational responsibilities. This Program Project will involve four interrelated research projects supported by two core facilities. Dr. Breakefield will serve as the Program Director and liaison between laboratories. She will be assisted in administrative responsibilities by an experienced Grants manager, Ms. Robin Sobolewski. Dr. Breakefield will make all final decisions on the operations of the PSO after extensive discussions with involved individuals. Dr. Breakefield will be advised by an Internal Advisory Committee consisting of three senior members of the PPG: Dr. Pradeep Bhide, Dr. David Standaert and Dr. Laurie Ozelius, as well as two investigators at Partners (MGH/BWH) with related expertise - Dr. James Gusella (human generics and neurologic disease) and Dr. David Kwiatkowski (mouse models for neurologic disease and cell biology). Combination conference calls/onsite meetings will be held at least twice a year with this group as issues arise needing advice. This group will also be present at the External Advisory meeting. The functions of this committee will consist of critical review of key data, strategic guidance in planning future experiments and collaborations, advice on any conflicts that arise within the PPG group or with collaborators, and appropriate adjustments resulting from any changes in Pl status or their locations. Patient issues will be handled by the physician/scientists in the group, Drs. Nutan Sharma and David Standaert, as well as our collaborator. Dr. Susan Bressman, with genetic counseling issues covered by Drs. Sharma and Bressman, with assistance from Ms. Trisha Multhaupt-Buell, a Genetic Counselor in the Movement Disorder Clinic. Advice on research strategy and evaluation of progress will be undertaken in consultation with a standing External Advisory Committee on a yearly basis at a day-long meeting at MGH. This committee will consist of five individuals (two, James Gusella and David Kwiatkowski also serving as members of the Internal Advisory Committee) with combined expertise in human genetics, neuronal development, cell biology, mouse models and clinical aspects of dystonia. (According to NINDS guidelines the additional names of members of the committee and letters from them will be provided when the application is funded). A detailed progress report incorporating critiques from the external review prepared by the External Advisors and Internal non-PPG Advisors will be distributed to all investigators in the Center and incorporated into the progress report of the non-competitive continuation applications. The scientific oversight will be carried out primarily by Dr. Breakefield, who will advise investigators on strategic and technical issues, promote collaboration among projects, monitor the functions and effectiveness of core facilities, and assess the scientific quality and progress of the work. This will require active interactions with all groups. Dr. Breakefield will confer with other members of the PSO on a weekly/monthly basis through informal discussions of progress and strategy via direct contact (Drs. Bhide, Sharma and Breakefield are located in adjacent space at MGH), phone calls, e-mail, tri-annual internal PSO meetings spread throughout each year, the annual External Advisor review and other national/international meetings attended by subsets of this group. In the annual progress reports we will include all interactions among Pis and collaborators in this PPG, as well as all attendees at the internal PPG meetings and External Reviews. To make sure there is ongoing exchange among Pis in the Northeast and Dr. Standaert in Georgia, in addition to the common meetings attended by Dr. Standaert and other Pis in this group, as well as biannual conference calls of the Internal Advisory Committee, we now plan to institute a monthly conference call among all Pis with exchange of data images using internet based technology for slide sharing (Glance.net). Through her close contacts with all the participants in this Center, Dr. Breakefield will be able to stimulate collaborative interactions and resolve potential conflicts before they arise. Given the high creativity and productivity of the investigators, their natural tendency to collaborate and their long track record of interaction and commitment to dystonia research, her main job will be to promote communication of research findings and sharing of reagents/resources within and among outside groups, and to guide investigators toward common foci and goals